Human Gene LRRK2 (uc001rmg.4)
  Description: Homo sapiens leucine-rich repeat kinase 2 (LRRK2), mRNA.
RefSeq Summary (NM_198578): This gene is a member of the leucine-rich repeat kinase family and encodes a protein with an ankryin repeat region, a leucine-rich repeat (LRR) domain, a kinase domain, a DFG-like motif, a RAS domain, a GTPase domain, a MLK-like domain, and a WD40 domain. The protein is present largely in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with Parkinson disease-8. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr12:40,618,813-40,763,086 Size: 144,274 Total Exon Count: 51 Strand: +
Coding Region
   Position: hg19 chr12:40,618,934-40,761,567 Size: 142,634 Coding Exon Count: 51 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:40,618,813-40,763,086)mRNA (may differ from genome)Protein (2527 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCLynxMalacardsMGI
neXtProtOMIMPubMedReactomeTreefamUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: LRRK2_HUMAN
DESCRIPTION: RecName: Full=Leucine-rich repeat serine/threonine-protein kinase 2; EC=2.7.11.1; AltName: Full=Dardarin;
FUNCTION: May play a role in the phosphorylation of proteins central to Parkinson disease. Phosphorylates PRDX3. May also have GTPase activity. Positively regulates autophagy through a calcium- dependent activation of the CaMKK/AMPK signaling pathway. The process involves activation of nicotinic acid adenine dinucleotide phosphate (NAADP) receptors, increase in lysosomal pH, and calcium release from lysosomes.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
SUBUNIT: Interacts with PARK2. Interacts with PRDX3. Interacts with TPCN2.
INTERACTION: O75581:LRP6; NbExp=3; IntAct=EBI-5323863, EBI-910915; Q13469:NFATC2; NbExp=3; IntAct=EBI-5323863, EBI-716258; O60260:PARK2; NbExp=3; IntAct=EBI-5323863, EBI-716346;
SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Mitochondrion. Note=Localized in the cytoplasm and associated with cellular membrane structures. Associates with the mitochondrial outer membrane.
TISSUE SPECIFICITY: Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.
DISEASE: Defects in LRRK2 are the cause of Parkinson disease type 8 (PARK8) [MIM:607060]. A slowly progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, postural instability, neuronal loss in the substantia nigra, and the presence of neurofibrillary MAPT (tau)-positive and Lewy bodies in some patients.
SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
SIMILARITY: Contains 12 LRR (leucine-rich) repeats.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 Roc domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/LRRK2";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LRRK2
CDC HuGE Published Literature: LRRK2
Positive Disease Associations: Alzheimer's disease; Parkinson's disease; progressive supranuclear palsy; dementia, frontotemporal; multiple system atropy , Crohn's disease , essential tremor , essential tremor Parkinson's disease , Neutrophils , Parkinson Disease , Parkinson's disease
Related Studies:
  1. Alzheimer's disease; Parkinson's disease; progressive supranuclear palsy; dementia, frontotemporal; multiple system atropy
    Hernandez, D. et al. 2005, The dardarin G 2019 S mutation is a common cause of Parkinson's disease but not other NEUROLOGICALenerative diseases., Neuroscience letters. 2005 Dec;389(3):137-9. [PubMed 16102903]
  2. Crohn's disease
    Barrett ,et al. 2008, Genome-wide assocation defines more than 30 distinct susceptibility loci for Crohn's disease, Nature genetics 2008 40- 8 : 955-62. [PubMed 18587394]
  3. essential tremor
    Deng, H. et al. 2006, The LRRK2 I2012T, G2019S and I2020T mutations are not common in patients with essential tremor, Neurosci Lett 2006. [PubMed 16939701]
    LRKK2 I2012T, G2019S and I2020T variants are rare causes of Caucasian ET.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: LRRK2
Diseases sorted by gene-association score: parkinson disease 8* (1316), hereditary late-onset parkinson disease* (175), parkinson disease, late-onset* (166), lrrk2-related parkinson disease* (119), snca-related parkinson disease (15), essential tremor (15), rem sleep behavior disorder (14), dementia, lewy body (13), multiple system atrophy (13), early-onset parkinson disease (11), movement disease (11), postencephalitic parkinson disease (10), parkinson disease 10 (10), supranuclear palsy, progressive (10), tremor (10), amyotrophic lateral sclerosis-parkinsonism/dementia complex (9), parkinson disease, juvenile, type 2* (8), athetosis (7), parkinson disease susceptibility (6), aphasia (6), dementia, frontotemporal (5), parkinson disease 15, autosomal recessive (4), lig4 syndrome (4), leprosy (3), synucleinopathy (2), nervous system disease (2), central nervous system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 15.75 RPKM in Lung
Total median expression: 155.02 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -61.70121-0.510 Picture PostScript Text
3' UTR -339.911519-0.224 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR020683 - Ankyrin_rpt-contain_dom
IPR011989 - ARM-like
IPR016024 - ARM-type_fold
IPR011009 - Kinase-like_dom
IPR001611 - Leu-rich_rpt
IPR025875 - Leu-rich_rpt_2_copies
IPR003591 - Leu-rich_rpt_typical-subtyp
IPR013684 - MIRO-like
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR020859 - ROC_GTPase
IPR008271 - Ser/Thr_kinase_AS
IPR005225 - Small_GTP-bd_dom
IPR001806 - Small_GTPase
IPR015943 - WD40/YVTN_repeat-like_dom
IPR001680 - WD40_repeat
IPR017986 - WD40_repeat_dom

Pfam Domains:
PF00025 - ADP-ribosylation factor family
PF00069 - Protein kinase domain
PF00071 - Ras family
PF07714 - Protein tyrosine kinase
PF08477 - Ras of Complex, Roc, domain of DAPkinase
PF12799 - Leucine Rich repeats (2 copies)
PF13516 - Leucine Rich repeat
PF13855 - Leucine rich repeat
PF16095 - C-terminal of Roc, COR, domain

SCOP Domains:
48371 - ARM repeat
101898 - NHL repeat
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50978 - WD40 repeat-like
69322 - Tricorn protease domain 2
50998 - Quinoprotein alcohol dehydrogenase-like
51004 - C-terminal (heme d1) domain of cytochrome cd1-nitrite reductase
52047 - RNI-like
52058 - L domain-like
52075 - Outer arm dynein light chain 1
52540 - P-loop containing nucleoside triphosphate hydrolases
56112 - Protein kinase-like (PK-like)
48403 - Ankyrin repeat

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2ZEJ - X-ray MuPIT 3D6T - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q5S007
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000149 SNARE binding
GO:0000166 nucleotide binding
GO:0003779 actin binding
GO:0003924 GTPase activity
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004708 MAP kinase kinase activity
GO:0005096 GTPase activator activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0005525 GTP binding
GO:0008017 microtubule binding
GO:0015631 tubulin binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0017048 Rho GTPase binding
GO:0017075 syntaxin-1 binding
GO:0030159 receptor signaling complex scaffold activity
GO:0030276 clathrin binding
GO:0034211 GTP-dependent protein kinase activity
GO:0036479 peroxidase inhibitor activity
GO:0039706 co-receptor binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0044325 ion channel binding
GO:0051018 protein kinase A binding
GO:1904713 beta-catenin destruction complex binding

Biological Process:
GO:0000165 MAPK cascade
GO:0000186 activation of MAPKK activity
GO:0000187 activation of MAPK activity
GO:0001933 negative regulation of protein phosphorylation
GO:0001934 positive regulation of protein phosphorylation
GO:0006468 protein phosphorylation
GO:0006897 endocytosis
GO:0006914 autophagy
GO:0006979 response to oxidative stress
GO:0007005 mitochondrion organization
GO:0007030 Golgi organization
GO:0007040 lysosome organization
GO:0007283 spermatogenesis
GO:0007528 neuromuscular junction development
GO:0008340 determination of adult lifespan
GO:0009267 cellular response to starvation
GO:0010468 regulation of gene expression
GO:0010506 regulation of autophagy
GO:0010508 positive regulation of autophagy
GO:0010738 regulation of protein kinase A signaling
GO:0010955 negative regulation of protein processing
GO:0010977 negative regulation of neuron projection development
GO:0014041 regulation of neuron maturation
GO:0016242 negative regulation of macroautophagy
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0019722 calcium-mediated signaling
GO:0021756 striatum development
GO:0021772 olfactory bulb development
GO:0022028 tangential migration from the subventricular zone to the olfactory bulb
GO:0030154 cell differentiation
GO:0031398 positive regulation of protein ubiquitination
GO:0032091 negative regulation of protein binding
GO:0032092 positive regulation of protein binding
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0033160 positive regulation of protein import into nucleus, translocation
GO:0034260 negative regulation of GTPase activity
GO:0034599 cellular response to oxidative stress
GO:0034613 cellular protein localization
GO:0035556 intracellular signal transduction
GO:0035564 regulation of kidney size
GO:0035640 exploration behavior
GO:0035641 locomotory exploration behavior
GO:0035751 regulation of lysosomal lumen pH
GO:0040012 regulation of locomotion
GO:0042391 regulation of membrane potential
GO:0043068 positive regulation of programmed cell death
GO:0043406 positive regulation of MAP kinase activity
GO:0043547 positive regulation of GTPase activity
GO:0046039 GTP metabolic process
GO:0046777 protein autophosphorylation
GO:0048312 intracellular distribution of mitochondria
GO:0048812 neuron projection morphogenesis
GO:0051646 mitochondrion localization
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0051900 regulation of mitochondrial depolarization
GO:0051966 regulation of synaptic transmission, glutamatergic
GO:0060070 canonical Wnt signaling pathway
GO:0060079 excitatory postsynaptic potential
GO:0060159 regulation of dopamine receptor signaling pathway
GO:0060161 positive regulation of dopamine receptor signaling pathway
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0061001 regulation of dendritic spine morphogenesis
GO:0070585 protein localization to mitochondrion
GO:0070997 neuron death
GO:0071287 cellular response to manganese ion
GO:0071407 cellular response to organic cyclic compound
GO:0072593 reactive oxygen species metabolic process
GO:0090140 regulation of mitochondrial fission
GO:0090263 positive regulation of canonical Wnt signaling pathway
GO:0090394 negative regulation of excitatory postsynaptic potential
GO:1900244 positive regulation of synaptic vesicle endocytosis
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901727 positive regulation of histone deacetylase activity
GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
GO:1902499 positive regulation of protein autoubiquitination
GO:1902692 regulation of neuroblast proliferation
GO:1902803 regulation of synaptic vesicle transport
GO:1902823 negative regulation of late endosome to lysosome transport
GO:1902902 negative regulation of autophagosome assembly
GO:1903125 negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation
GO:1903206 negative regulation of hydrogen peroxide-induced cell death
GO:1903215 negative regulation of protein targeting to mitochondrion
GO:1903217 negative regulation of protein processing involved in protein targeting to mitochondrion
GO:1903351 cellular response to dopamine
GO:1903980 positive regulation of microglial cell activation
GO:1904469 positive regulation of tumor necrosis factor secretion
GO:1904887 Wnt signalosome assembly
GO:1905279 regulation of retrograde transport, endosome to Golgi
GO:1905289 regulation of CAMKK-AMPK signaling cascade
GO:2000172 regulation of branching morphogenesis of a nerve
GO:2000300 regulation of synaptic vesicle exocytosis

Cellular Component:
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005743 mitochondrial inner membrane
GO:0005759 mitochondrial matrix
GO:0005764 lysosome
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0005794 Golgi apparatus
GO:0005798 Golgi-associated vesicle
GO:0005802 trans-Golgi network
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005902 microvillus
GO:0008021 synaptic vesicle
GO:0016020 membrane
GO:0016234 inclusion body
GO:0030054 cell junction
GO:0030424 axon
GO:0030425 dendrite
GO:0030426 growth cone
GO:0030672 synaptic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0031966 mitochondrial membrane
GO:0032473 cytoplasmic side of mitochondrial outer membrane
GO:0032839 dendrite cytoplasm
GO:0042995 cell projection
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:0043195 terminal bouton
GO:0043204 perikaryon
GO:0043231 intracellular membrane-bounded organelle
GO:0044753 amphisome
GO:0044754 autolysosome
GO:0045121 membrane raft
GO:0045202 synapse
GO:0070062 extracellular exosome
GO:0097487 multivesicular body, internal vesicle
GO:0098794 postsynapse
GO:0099400 caveola neck
GO:1990904 ribonucleoprotein complex
GO:1990909 Wnt signalosome


-  Descriptions from all associated GenBank mRNAs
  JA482232 - Sequence 215 from Patent WO2011072091.
JE980524 - Sequence 215 from Patent EP2862929.
LP895247 - Sequence 111 from Patent EP3253886.
BC117180 - Homo sapiens leucine-rich repeat kinase 2, mRNA (cDNA clone MGC:150789 IMAGE:40125731), complete cds.
AY792511 - Homo sapiens leucine-rich repeat kinase 2 (LRRK2) mRNA, complete cds.
AK127729 - Homo sapiens cDNA FLJ45829 fis, clone NT2RP8006452.
JA537589 - Sequence 101 from Patent WO2011114106.
JA537591 - Sequence 103 from Patent WO2011114106.
AL832453 - Homo sapiens mRNA; cDNA DKFZp451G151 (from clone DKFZp451G151).
JD500098 - Sequence 481122 from Patent EP1572962.
JD261655 - Sequence 242679 from Patent EP1572962.
JD048742 - Sequence 29766 from Patent EP1572962.
JD288374 - Sequence 269398 from Patent EP1572962.
JD291666 - Sequence 272690 from Patent EP1572962.
JD081768 - Sequence 62792 from Patent EP1572962.
AK131537 - Homo sapiens cDNA FLJ16769 fis, clone BRAWH3022866.
AK122640 - Homo sapiens cDNA FLJ16068 fis, clone HLUNG2000751, weakly similar to MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 9 (EC 2.7.1.-).
JA537590 - Sequence 102 from Patent WO2011114106.
AL834529 - Homo sapiens mRNA; cDNA DKFZp434H2111 (from clone DKFZp434H2111).
BX640975 - Homo sapiens mRNA; cDNA DKFZp686E15222 (from clone DKFZp686E15222).
AK026776 - Homo sapiens cDNA: FLJ23123 fis, clone LNG08039.
JD311251 - Sequence 292275 from Patent EP1572962.
JD110061 - Sequence 91085 from Patent EP1572962.
JD314919 - Sequence 295943 from Patent EP1572962.
JD039830 - Sequence 20854 from Patent EP1572962.
JD392429 - Sequence 373453 from Patent EP1572962.
JD297058 - Sequence 278082 from Patent EP1572962.
JD519931 - Sequence 500955 from Patent EP1572962.
JD237895 - Sequence 218919 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05012 - Parkinson's disease

Reactome (by CSHL, EBI, and GO)

Protein Q5S007 (Reactome details) participates in the following event(s):

R-HSA-8857565 Phosphorylated GPNMB recruits PTK6 and LRRK2 in the presence of LINC01139
R-HSA-8857577 LINC01139 facilitates PTK6 autophosphorylation
R-HSA-8857583 LINC01139 promotes phosphorylation of HIF1A by PTK6 and LRRK2
R-HSA-8857538 PTK6 promotes HIF1A stabilization
R-HSA-8848021 Signaling by PTK6
R-HSA-9006927 Signaling by Non-Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A6NJU2, LRRK2_HUMAN, NM_198578, NP_940980, PARK8, Q5S007, Q6ZS50, Q8NCX9
UCSC ID: uc001rmg.4
RefSeq Accession: NM_198578
Protein: Q5S007 (aka LRRK2_HUMAN)
CCDS: CCDS31774.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene LRRK2:
lrrk2 (LRRK2 Parkinson Disease)
parkinson-overview (Parkinson Disease Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_198578.3
exon count: 51CDS single in 3' UTR: no RNA size: 9239
ORF size: 7584CDS single in intron: no Alignment % ID: 99.99
txCdsPredict score: 14862.50frame shift in genome: no % Coverage: 99.84
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.